According to the U S Department of Health
According to the 2014 U.S. Department of Health report, smoking could significantly increase the overall and specific mortality rates among cancer patients and survivors, as well as the risk of secondary primary tumours 3 . Smoking continuation after initial diagnosis has various epidemiological and genetic factors. If we could find the specific factors that influence the failure of smoking cessation, we could conduct targeted intervention, and then the objective of accurate smoking cessation can be achieved. Our previous results showed that pain, quit attempts and sleep quality were significantly correlated with the Fagerstrom Test for Nicotine Dependence (FTND) scores. However, all of the factors could explain part of the failure reasons for smoking cessation. One-third of smokers failed to quit smoking without clear explanations.
Failure to quit smoking (defined as nicotine dependence) is significantly related to genetic status. Several studies reported that single nucleotide polymorphisms (SNPs) of the nicotinic Adriamycin receptor alpha 4 subunits (CHRNA4) were significantly associated with nicotine dependence 4-8. For example, a retrospective study including 348 patients with smoking nicotine tolerance score > 4 showed that CHRNA4 (rs2229959 and rs1044396), CHRNB2, brain-derived neurotrophic factor and neurotrophic tyrosine kinase receptor 2 were independently associated with nicotine dependence9. Lior et al. showed that CHRNA5 (rs588765 and rs16969968) and CHRNA3 (rs578776) were significantly associated with patients' nicotine dependence and the onset time of Parkinson's disease10. Chen et al.'s study also reported that the CHRNA5-A3-B4 nicotine receptor gene was associated with nicotine dependence and psychological disorders11. Although these studies examined the different types of nicotine dependence on related genes, they did not further divide the patients into different groups according to the actual smoking condition after cancer diagnosis. Moreover, they did not explore the impact of SNPs of these genes on the nicotine dependence of patients with lung cancer.
Considering the significant role of smoking in the development and progression of lung cancer, it is necessary to investigate the relationship between the abovementioned gene SNPs and nicotine dependence in patients with lung cancer and their role in the failure to quit smoking after lung cancer diagnosis. The current study will provide the basis of the genetic classification for building a health management model of quitting smoking for patients with lung cancer.
Methods Patient cohort
Patients with histologically or pathologically diagnosed lung cancer from Shanghai Pulmonary Hospital were included in this study from July 2017 to March 2018. According to the actual smoking condition, patients were divided into the never smoking group, failure of smoking cessation group and success of smoking cessation group. Smokers are defined as those who answer that deuterostomes are
still smoking or that they are not smoking at present, but urinary cotinine level is equal or higher than previous level; never smokers are defined as those who do not smoke or take tobacco or nicotine substitutes; regular smokers are defined as those who smoke at least one cigarette a week for more than three months12; quit smoking success is defined as regular smokers who have quit smoking one or more times and who did not relapse for more than one year until the time of investigation. Quit smoking failure is defined as regular smokers who have quit smoking one or more times, but there still relapsed within one year at the time of investigation13. A minimal input of smoking to join the study was people who smoked at least one cigarette a week for more than three months. Patients who stopped smoking after lung cancer diagnosis were eligible, and those who quit smoking before the initial diagnosis were excluded. The ethics committee of the Shanghai Pulmonary Hospital, China, approved the study protocol (No. k17-121). Questionnaires and definitions
Demographic data, including gender, age, marital status, education level, annual household income, occupations, pathological types of lung cancer, and lung cancer stage, were recorded. Smoking status included years of regular smoking, initial age of smoking and cigarette consumption.
FTND was used to assess physical nicotine dependence. The FTND contains six items that evaluate the quantity of cigarettes smoked, diurnal patterns of use (time to first cigarette upon awakening, smoking more during the first 2 hours of the day, the cigarette one would hate most to give up), and impaired control over use (smoking when ill, difficulty refraining from smoking when prohibited). Total scores range from 0 to 10. We classified nicotine dependence into two categories: low dependence (LD; FTND score < 4) and high dependence (HD; FTND score ≥ 4) 14. Cronbach internal consistency coefficients of FTND items for participants α = 0.75 15.